2-219295006-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002846.4(PTPRN):c.2644G>A(p.Ala882Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,604,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PTPRN
NM_002846.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

Publications

2 publications found

Variant links:

Genes affected

PTPRN (HGNC:9676): (protein tyrosine phosphatase receptor type N) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and a single catalytic domain, and thus represents a receptor-type PTP. This PTP was found to be an autoantigen that is reactive with insulin-dependent diabetes mellitus (IDDM) patient sera, and thus may be a potential target of autoimmunity in diabetes mellitus. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Dec 2010]

PTPRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.093863875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRN	NM_002846.4 link	c.2644G>A	p.Ala882Thr	missense_variant	Exon 19 of 23	ENST00000295718.7	NP_002837.1	Q16849-1Q96IA0
PTPRN	NM_001199763.2 link	c.2557G>A	p.Ala853Thr	missense_variant	Exon 18 of 22		NP_001186692.1	Q16849-2
PTPRN	NM_001199764.2 link	c.2374G>A	p.Ala792Thr	missense_variant	Exon 19 of 23		NP_001186693.1	Q16849-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRN	ENST00000295718.7 link	c.2644G>A	p.Ala882Thr	missense_variant	Exon 19 of 23	1	NM_002846.4	ENSP00000295718.2		Q16849-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000214

AC:

AN:

233896

AF XY:

0.0000314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000289

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1452558

Hom.:

Cov.:

AF XY:

0.00000969

AC XY:

AN XY:

722252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32662

American (AMR)

AF:

0.00

AC:

AN:

43874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25818

East Asian (EAS)

AF:

0.000410

AC:

AN:

39004

South Asian (SAS)

AF:

0.00

AC:

AN:

84758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108094

Other (OTH)

AF:

0.00

AC:

AN:

59914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 31, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2644G>A (p.A882T) alteration is located in exon 19 (coding exon 19) of the PTPRN gene. This alteration results from a G to A substitution at nucleotide position 2644, causing the alanine (A) at amino acid position 882 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.16

.;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.046

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.094

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-0.11

.;N;.

PhyloP100

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

0.48

N;N;.

REVEL

Benign

0.19

Sift

Benign

0.64

T;T;.

Sift4G

Benign

0.79

T;T;T

Polyphen

0.0040

.;B;.

Vest4

0.24

MutPred

0.27

.;Gain of phosphorylation at A882 (P = 0.0285);.;

MVP

0.77

MPC

0.43

ClinPred

0.085

GERP RS

4.2

Varity_R

0.10

gMVP

0.18

Mutation Taster

=41/59

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-219295006-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over